The structural relationship/of human apoB-100 and apoB-48 have been elucidated by sequence analysis of cDNA clones of apoB-100 mRNA. Clones were obtained which contained a C more than T substitution at nucleotide 6666 in the apoB-100 cDNA. The C more than T substitution converted the 'CAA' codon for glutamine in apoB-100 into a `TAA' premature stop codon. The change in the `CAA' codon for glutamine for the 'TAA' stop codon resulted in the termination of translation at amino acid 2152. Therefore apoB-100 contained 4536 amino acids, and apoB-48 contained 2152 amino acids. The C more than T change was not present at the DNA level, and the mechanism for the production of apoB-48 is a unique RNA editing mechanism which has not been previously described. The RNA editing mechanism for apoB-48 biosynthesis was shown to be present in both the liver and intestine in the human as well as the rat. A detailed analysis of the 5' regulatory region of the apoA-I gene has been performed. TATA box, CAT box like, and two GC sequences were identified. Both promotors as well as tissue specific repressors of apoA-I expression in non-apoA-I producing cells were present in the 5' flanking region of the apoA-I gene.